Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

被引：0
|
作者：
Ma, Yanyu [1 ]
Song, Yidan [1 ]
Wang, Junyi [1 ]
Shi, Xiayu [1 ]
Yuan, Zhen [1 ]
Li, Shuang [1 ]
Li, Honglin [1 ,2 ,3 ]
Chen, Zhuo [1 ]
Li, Shiliang [1 ,2 ]
机构：
[1] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai, Peoples R China
[2] East China Normal Univ, Innovat Ctr AI & Drug Discovery, Shanghai 200062, Peoples R China
[3] Lingang Lab, Shanghai 200031, Peoples R China
来源：
FUTURE MEDICINAL CHEMISTRY | 2024年 / 16卷 / 07期
基金：
中国国家自然科学基金;
关键词：
cancer treatment; covalent inhibitor; DJ-1; molecular docking; virtual screening; THERAPEUTIC TARGET; ANDROGEN RECEPTOR; CRYSTAL-STRUCTURE; PROTEIN; EXPRESSION; APOPTOSIS; DOCKING; BINDING; CANCER;
D O I：
10.4155/fmc-2023-0301
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 mu M and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.
引用
收藏
页码：665 / 677
页数：14
相关论文
共 50 条
  • [21] Discovery of novel MSK1 inhibitors with hybrid virtual screening and structure-based drug design
    Huang, Zunnan
    Liu, Kangdong
    Bode, Ann M.
    Dong, Zigang
    CANCER RESEARCH, 2011, 71
  • [22] Discovery of Novel DUSP4 Inhibitors through the Virtual Screening with Docking Simulations
    Park, Hwangseo
    Jeon, Tae Jin
    Pham Ngoc Chien
    Park, So Ya
    Oh, Sung Min
    Kim, Seung Jun
    Ryu, Seong Eon
    BULLETIN OF THE KOREAN CHEMICAL SOCIETY, 2014, 35 (09) : 2655 - 2659
  • [23] Discovery of novel 5'-methylthioadenosine nucleosidase inhibitors by virtual screening 1 and bioassays
    Chen, Shuangkou
    Tan, Xiaoqing
    Tang, Si
    Xu, Mingxin
    Xu, Xi
    Ren, Fengming
    Yang, Zhenning
    JOURNAL OF MOLECULAR STRUCTURE, 2022, 1270
  • [24] A NOVEL ROLE FOR DJ-1 IN CARDIOPROTECTION
    Mukherjee, U. A.
    Ong, S. B.
    Davidson, S. M.
    Yellon, D. M.
    Hausenloy, D. J.
    HEART, 2011, 97 (24)
  • [25] Discovery of Novel Inhibitors of HIV-1 Reverse Transcriptase Through Virtual Screening of Experimental and Theoretical Ensembles
    Ivetac, Anthony
    Swift, Sara E.
    Boyer, Paul L.
    Diaz, Arturo
    Naughton, John
    Young, John A. T.
    Hughes, Stephen H.
    McCammon, J. Andrew
    CHEMICAL BIOLOGY & DRUG DESIGN, 2014, 83 (05) : 521 - 531
  • [26] Discovery of Immunoproteasome Inhibitors Using Large-Scale Covalent Virtual Screening
    Scarpino, Andrea
    Bajusz, David
    Proj, Matic
    Gobec, Martina
    Sosic, Izidor
    Gobec, Stanislav
    Ferenczy, Gyoergy G.
    Keseru, Gyoergy M.
    MOLECULES, 2019, 24 (14):
  • [27] Transcriptional Activation of the Cholecystokinin Gene by DJ-1 through Interaction of DJ-1 with RREB1 and the Effect of DJ-1 on the Cholecystokinin Level in Mice
    Yamane, Takuya
    Suzui, Sayaka
    Kitaura, Hirotake
    Takahashi-Niki, Kazuko
    Iguchi-Ariga, Sanae M. M.
    Ariga, Hiroyoshi
    PLOS ONE, 2013, 8 (11):
  • [28] Discovery of VEGFR inhibitors through virtual screening and energy assessment
    Reang, Jurnal
    Sharma, Kalicharan
    Sharma, Prabodh C.
    Yadav, Vivek
    Sharma, Vinita
    Majeed, Jaseela
    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2023, 37 (05)
  • [29] Novel Virtual Screening Approach for the Discovery of Human Tyrosinase Inhibitors
    Ai, Ni
    Welsh, William J.
    Santhanam, Uma
    Hu, Hong
    Lyga, John
    PLOS ONE, 2014, 9 (11):
  • [30] Discovery of Entamoeba histolytica hexokinase 1 inhibitors through homology modeling and virtual screening
    Leticia Saucedo-Mendiola, Maria
    Manuel Salas-Pacheco, Jose
    Najera, Hugo
    Rojo-Dominguez, Arturo
    Yepez-Mulia, Lilian
    Avitia-Dominguez, Claudia
    Tellez-Valencia, Alfredo
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2014, 29 (03) : 325 - 332
12345